This project is designed to provide the opportunity for in vivo evaluation, including infectivity and titration studies, of a variety of primate lentiviruses that will subsequently be used in other related experiments. In one experiment the virus HIV-2287, which has been well characterized in vivo in Macaca nemestrina, was inoculated into M. fascicularis and M. mulatta, as a test of species variation in infectivity and pathogenesis. After intravenous inoculation with 1,000 TCID of virus (equivalent to 100 animal infectious doses in M. nemestrina), M. fascicularis became infected and showed depletion of circulating CD4+ cells similar to M. nemestrina. The virus also infected M. mulatta, but at much lower levels, and there was no evidence of pathogenesis. This evidence of species variation is an important consideration in the design and testing of vaccines and therapeutics. In another experiment, the virus SHIV229, derived from a series of in vivo passages of SHIVHXBc 2, w as titrated in vivo to determine the minimal infectious dose with intravenous inoculation. It was found that doses from 100 TCID down to 0.1 TCID were infectious and pathogenic, producing depletion of CD4+ cells within 2-4 weeks. The single monkey inoculated at the dose of 0.01 TCID was not infected. A third experiment was an in vivo titration for the minimal infectious dose for intrarectal inoculation. Two M. nemestrina were inoculated with 1000 TCID intrarectally; two others were inoculated with 10 TCID. One of the pair inoculated at the higher dose became infected, and neither of the pair inocuated at the lower dose was infected. This experiment will be expanded to refine the determination of this minimal infectious dose, prior to the use of this SHIV229 virus stock as a challenge for vaccine or therapeutic studies. FUNDING NIH grant RR00166 and NIAID [SVEU].